Recent evidence indicates that rosiglitazone, a potent agonist of peroxisome proliferator-activated receptor gamma (PPARγ), can prevent or attenuate neurodegeneration in Alzheimers Disease (AD), but the underlying mechanisms remain to be fully elucidated.In this study, we examined the effects of soluble amyloid-β protein (Aβ) oligomers and rosiglitazone on the synaptic development and synaptic plasticity in rat hippocampal slices using live cell imaging and electrophysiological recording.We found that the incubation of hippocampal cultures with A β42 oligomers (500 nM) for 3 h significantly decreased dendritic filopodia and spine density.Pretreatment with rosiglitazone (0.5-5 μM) for 24 hrs rescued the Aβ42-induced loss of dendritic filopodia and spines in a dose-dependent manner.However, neither Aβ42 oligomers nor rosiglitazone has significant effect on the velocity and length of dendritic filopodia.The beneficial effect of rosiglitazone was abolished by the PPARγ-specific antagonist, GW9622.Electrophysiological recording showed that acute exposure of slices with 500 nM Aβ42 oligomers for 40 min impaired high frequency stimulation-induced hippocampal long term potentiation (LTP)in dentate gyrus region.Interestingly, pre-incubation of hippocampal slices with rosiglitazone significantly rescued the Aβ42-induced LTP deficit, which depended on rosiglitazone concentrations (1-5 pM) and pretreated period (1-5h).In conclusion, our data suggest that rosiglitazone rescues Aβ42 oligomers-induced synaptic function impairment through the PPARγ-dependent pathway in a concentration and time dependent manner.This study provides novel insights into the mechanisms for the beneficial effect of rosiglitzone in AD patients.